Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis
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The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment.
Material and methods
One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment.
After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment.
We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.
KeywordsGlucose Cholesterol Triglycerides Weight gain Medication-naïve Second-generation antipsychotic
This study was conducted as part of a clinical trial “Comparative Study of Aripiprazole, Quetiapine and Ziprasidone in the Treatment of First Episode Non-affective Psychosis (AZQ2005).” ClinicalTrials.gov Identifier: NCT02305823.
The authors wish to thank all “Programa Asistencial de las Fases Iniciales de Psicosis” (PAFIP) research team and all patients and family members who participated in the study.
BC-F designed the study and wrote the protocol. PSP evaluated the patients and collected the study variables. VO-G built and maintained the database and helped with the statistical analyses. RP-I and JV-B managed the literature searches. JV-B undertook the statistical analysis and wrote the first draft of the manuscript. ADM, RP-I, and BC-F contributed to the interpretation of the data and revised the manuscript critically. All authors contributed to and have approved the final manuscript.
The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005–0308007; and Fundación Marqués de Valdecilla API07/011. Unrestricted educational and research grants from AstraZeneca, Pfizer, Bristol-Myers Squibb, and Johnson & Johnson provided support for PAFIP activities. No pharmaceutical industry or institutional sponsors participated in the study concept and design, data collection, analysis and interpretation of the results, and drafting the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- Andreasen N (1983) Scale for the assessment of negative symptoms (SANS). University of Iowa, Iowa CityGoogle Scholar
- Andreasen N (1984) Scale for the assessment of positive symptoms (SAPS). University of Iowa, Iowa CityGoogle Scholar
- Carvalho AF, Sharma MS, Brunoni AR et al (2016) The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother. Psychosomatics 85(5):270–288Google Scholar
- Foley DL and Morley KI (2011) Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry 68:609–616Google Scholar
- Hjorthøj C, Stürup AE, McGrath JJ et al (2017) Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry 4(4):295–301Google Scholar
- Jensen KG, Correll CU, Rudå D et al (2017) Pretreatment cardiometabolic status in youth with early-onset psychosis: baseline results from the TEA trial. J Clin Psychiatry. https://doi.org/10.4088/JCP.15m10479
- Karayal ON, Glue P, Bachinsky M et al (2011) Switching from quetiapine to ziprasidone: a sixteen-week, open-label, multicenter study evaluating the effectiveness and safety of ziprasidone in outpatient subjects with schizophrenia or schizoaffective disorder. J Psychiatr Pract 17(2):100–109CrossRefPubMedGoogle Scholar
- Kerwin R, Millet B, Herman E et al (2007) A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study. Eur Psychiatry 22:433–443CrossRefPubMedGoogle Scholar
- Komossa K, Rummel-Kluge C, Hunger H et al (2009) Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 4:CD006627Google Scholar
- Mackin P, Waton T, Watkinson HM et al (2012) A four-year naturalistic prospective study of cardiometabolic disease in antipsychotic-treated patients. Eur Psychiatry 27(1):50–5Google Scholar
- Malla A, Mustafa S, Rho A et al (2016) Therapeutic effectiveness and tolerability of aripiprazole as initial choice of treatment in first episode psychosis in an early intervention service: a one-year outcome study. Schizophr Res 174(1–3):120–125. https://doi.org/10.1016/j.schres.2016.04.036 CrossRefPubMedGoogle Scholar
- Pelayo-Terán JM, Pérez-Iglesias R, Ramírez-Bonilla M et al (2008) Epidemiological factors associated with treated incidence of first-episode non-affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis. Early Interv Psychiatry 2(3):178–187CrossRefPubMedGoogle Scholar
- Pérez-Iglesias R, Martínez-García O, Pardo-Garcia G et al (2014b) Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors. Int J Neuropsychopharmacol 17(1):41–51CrossRefPubMedGoogle Scholar
- Stahl SM, Mignon L, Meyer JM (2009) Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand 119(3):171–9Google Scholar
- Stroup TS, McEvoy JP, Ring KD et al (2011) A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry 168:947–956CrossRefPubMedPubMedCentralGoogle Scholar
- Zhai D, Lang Y, Feng Y et al (2017) Early onset of cardiometabolic risk factor profiles in drug naïve adolescents and young adults with first-episode schizophrenia. Schizophr Res pii: S0920-9964(17):30126–30123Google Scholar